Glucagon-like peptide-1 receptor (GLP-1R) agonists are now commonly used to treat
type 2 diabetes and obesity. GLP-1R signaling in the spinal cord has been suggested
to account for the mild tachycardia caused by GLP-1R agonists, and may also be involved
in the therapeutic effects of these drugs. However, the neuroanatomy of the GLP-1/GLP-1R
system in the spinal cord is still poorly understood. Here we applied in situ hybridization
and immunohistochemistry to characterize this system, and its relation to cholinergic
neurons. GLP-1R transcript and protein were expressed in neuronal cell bodies across
the gray matter, in matching distribution patterns. GLP-1R-immunolabeling was also
robust in dendrites and axons, especially in laminae II–III in the dorsal horn. Cerebrospinal
fluid-contacting neurons expressed GLP-1R protein at exceedingly high levels. Only
small subpopulations of cholinergic neurons expressed GLP-1R, including a subset of
sympathetic preganglionic neurons at the rostral tip of the intermediolateral nucleus.
GLP-1 axons innervated all regions where GLP-1R neurons were distributed, except laminae
II–III. Scattered preproglucagon ( Gcg ) mRNA-expressing neurons were identified in
the cervical and lumbar enlargements. The results will facilitate further studies
on how GLP-1 regulates the sympathetic system and other autonomic and somatic functions
via the spinal cord.
